Ehsan Samei

Fakrul Islam Tushar, Ehsan Abadi, Saman Sotoudeh-Paima et al.

Research studies of artificial intelligence models in medical imaging have been hampered by poor generalization. This problem has been especially concerning over the last year with numerous applications of deep learning for COVID-19 diagnosis. Virtual imaging trials (VITs) could provide a solution for objective evaluation of these models. In this work utilizing the VITs, we created the CVIT-COVID dataset including 180 virtually imaged computed tomography (CT) images from simulated COVID-19 and normal phantom models under different COVID-19 morphology and imaging properties. We evaluated the performance of an open-source, deep-learning model from the University of Waterloo trained with multi-institutional data and an in-house model trained with the open clinical dataset called MosMed. We further validated the model's performance against open clinical data of 305 CT images to understand virtual vs. real clinical data performance. The open-source model was published with nearly perfect performance on the original Waterloo dataset but showed a consistent performance drop in external testing on another clinical dataset (AUC=0.77) and our simulated CVIT-COVID dataset (AUC=0.55). The in-house model achieved an AUC of 0.87 while testing on the internal test set (MosMed test set). However, performance dropped to an AUC of 0.65 and 0.69 when evaluated on clinical and our simulated CVIT-COVID dataset. The VIT framework offered control over imaging conditions, allowing us to show there was no change in performance as CT exposure was changed from 28.5 to 57 mAs. The VIT framework also provided voxel-level ground truth, revealing that performance of in-house model was much higher at AUC=0.87 for diffuse COVID-19 infection size >2.65% lung volume versus AUC=0.52 for focal disease with <2.65% volume. The virtual imaging framework enabled these uniquely rigorous analyses of model performance.

Fakrul Islam Tushar, Husam Nujaim, Wanyi Fu et al.

Organ segmentation of medical images is a key step in virtual imaging trials. However, organ segmentation datasets are limited in terms of quality (because labels cover only a few organs) and quantity (since case numbers are limited). In this study, we explored the tradeoffs between quality and quantity. Our goal is to create a unified approach for multi-organ segmentation of body CT, which will facilitate the creation of large numbers of accurate virtual phantoms. Initially, we compared two segmentation architectures, 3D-Unet and DenseVNet, which were trained using XCAT data that is fully labeled with 22 organs, and chose the 3D-Unet as the better performing model. We used the XCAT-trained model to generate pseudo-labels for the CT-ORG dataset that has only 7 organs segmented. We performed two experiments: First, we trained 3D-UNet model on the XCAT dataset, representing quality data, and tested it on both XCAT and CT-ORG datasets. Second, we trained 3D-UNet after including the CT-ORG dataset into the training set to have more quantity. Performance improved for segmentation in the organs where we have true labels in both datasets and degraded when relying on pseudo-labels. When organs were labeled in both datasets, Exp-2 improved Average DSC in XCAT and CT-ORG by 1. This demonstrates that quality data is the key to improving the model's performance.

Fakrul Islam Tushar, Lavsen Dahal, Saman Sotoudeh-Paima et al.

Purpose: The credibility of Artificial Intelligence (AI) models for medical imaging continues to be a challenge, affected by the diversity of models, the data used to train the models, and applicability of their combination to produce reproducible results for new data. In this work, we aimed to explore whether emerging Virtual Imaging Trials (VIT) methodologies can provide an objective resource to approach this challenge. Approach: The study was conducted for the case example of COVID-19 diagnosis using clinical and virtual computed tomography (CT) and chest radiography (CXR) processed with convolutional neural networks. Multiple AI models were developed and tested using 3D ResNet-like and 2D EfficientNetv2 architectures across diverse datasets. Results: Model performance was evaluated using the area under the curve (AUC) and the DeLong method for AUC confidence intervals. The models trained on the most diverse datasets showed the highest external testing performance, with AUC values ranging from 0.73-0.76 for CT and 0.70-0.73 for CXR. Internal testing yielded higher AUC values (0.77-0.85 for CT and 0.77-1.0 for CXR), highlighting a substantial drop in performance during external validation, which underscores the importance of diverse and comprehensive training and testing data. Most notably, the VIT approach provided objective assessment of the utility of diverse models and datasets, while offering insight into the influence of dataset characteristics, patient factors, and imaging physics on AI efficacy. Conclusions: The VIT approach enhances model transparency and reliability, offering nuanced insights into the factors driving AI performance and bridging the gap between experimental and clinical settings.

Kaouther Mouheb, Mobina Ghojogh Nejad, Lavsen Dahal et al.

Accurate 3D modeling of human organs is critical for constructing digital phantoms in virtual imaging trials. However, organs such as the large intestine remain particularly challenging due to their complex geometry and shape variability. We propose CLAP, a novel Conditional LAtent Point-diffusion model that combines geometric deep learning with denoising diffusion models to enhance 3D representations of the large intestine. Given point clouds sampled from segmentation masks, we employ a hierarchical variational autoencoder to learn both global and local latent shape representations. Two conditional diffusion models operate within this latent space to refine the organ shape. A pretrained surface reconstruction model is then used to convert the refined point clouds into meshes. CLAP achieves substantial improvements in shape modeling accuracy, reducing Chamfer distance by 26% and Hausdorff distance by 36% relative to the initial suboptimal shapes. This approach offers a robust and extensible solution for high-fidelity organ modeling, with potential applicability to a wide range of anatomical structures.

Fakrul Islam Tushar, Ehsan Samei, Cynthia Rudin et al.

Objective: Although medical imaging datasets are increasingly available, abnormal and annotation-intensive findings critical to lung cancer screening, particularly small pulmonary nodules, remain underrepresented and inconsistently curated. Methods: We introduce NodMAISI, an anatomically constrained, nodule-oriented CT synthesis and augmentation framework trained on a unified multi-source cohort (7,042 patients, 8,841 CTs, 14,444 nodules). The framework integrates: (i) a standardized curation and annotation pipeline linking each CT with organ masks and nodule-level annotations, (ii) a ControlNet-conditioned rectified-flow generator built on MAISI-v2's foundational blocks to enforce anatomy- and lesion-consistent synthesis, and (iii) lesion-aware augmentation that perturbs nodule masks (controlled shrinkage) while preserving surrounding anatomy to generate paired CT variants. Results: Across six public test datasets, NodMAISI improved distributional fidelity relative to MAISI-v2 (real-to-synthetic FID range 1.18 to 2.99 vs 1.69 to 5.21). In lesion detectability analysis using a MONAI nodule detector, NodMAISI substantially increased average sensitivity and more closely matched clinical scans (IMD-CT: 0.69 vs 0.39; DLCS24: 0.63 vs 0.20), with the largest gains for sub-centimeter nodules where MAISI-v2 frequently failed to reproduce the conditioned lesion. In downstream nodule-level malignancy classification trained on LUNA25 and externally evaluated on LUNA16, LNDbv4, and DLCS24, NodMAISI augmentation improved AUC by 0.07 to 0.11 at <=20% clinical data and by 0.12 to 0.21 at 10%, consistently narrowing the performance gap under data scarcity.

Fakrul Islam Tushar, Avivah Wang, Lavsen Dahal et al.

Background: Development of artificial intelligence (AI) models for lung cancer screening requires large, well-annotated low-dose computed tomography (CT) datasets and rigorous performance benchmarks. Purpose: To create a reproducible benchmarking resource leveraging the Duke Lung Cancer Screening (DLCS) and multiple public datasets to develop and evaluate models for nodule detection and classification. Materials & Methods: This retrospective study uses the DLCS dataset (1,613 patients; 2,487 nodules) and external datasets including LUNA16, LUNA25, and NLST-3D. For detection, MONAI RetinaNet models were trained on DLCS (DLCS-De) and LUNA16 (LUNA16-De) and evaluated using the Competition Performance Metric (CPM). For nodule-level classification, we compare five strategies: pretrained models (Models Genesis, Med3D), a self-supervised foundation model (FMCB), and ResNet50 with random initialization versus Strategic Warm-Start (ResNet50-SWS) pretrained with detection-derived candidate patches stratified by confidence. Results: For detection on the DLCS test set, DLCS-De achieved sensitivity 0.82 at 2 false positives/scan (CPM 0.63) versus LUNA16-De (0.62, CPM 0.45). For external validation on NLST-3D, DLCS-De (sensitivity 0.72, CPM 0.58) also outperformed LUNA16-De (sensitivity 0.64, CPM 0.49). For classification across multiple datasets, ResNet50-SWS attained AUCs of 0.71 (DLCS; 95% CI, 0.61-0.81), 0.90 (LUNA16; 0.87-0.93), 0.81 (NLST-3D; 0.79-0.82), and 0.80 (LUNA25; 0.78-0.82), matching or exceeding pretrained/self-supervised baselines. Performance differences reflected dataset label standards. Conclusion: This work establishes a standardized benchmarking resource for lung cancer AI research, supporting model development, validation, and translation. All code, models, and data are publicly released to promote reproducibility.

Fakrul Islam Tushar, Lavsen Dahal, Cindy McCabe et al.

AI models for lung cancer screening are limited by data scarcity, impacting generalizability and clinical applicability. Generative models address this issue but are constrained by training data variability. We introduce SYN-LUNGS, a framework for generating high-quality 3D CT images with detailed annotations. SYN-LUNGS integrates XCAT3 phantoms for digital twin generation, X-Lesions for nodule simulation (varying size, location, and appearance), and DukeSim for CT image formation with vendor and parameter variability. The dataset includes 3,072 nodule images from 1,044 simulated CT scans, with 512 lesions and 174 digital twins. Models trained on clinical + simulated data outperform clinical only models, achieving 10% improvement in detection, 2-9% in segmentation and classification, and enhanced synthesis. By incorporating anatomy-informed simulations, SYN-LUNGS provides a scalable approach for AI model development, particularly in rare disease representation and improving model reliability.

David Fenwick, Navid NaderiAlizadeh, Vahid Tarokh et al.

Protocol optimization is critical in Computed Tomography (CT) to achieve high diagnostic image quality while minimizing radiation dose. However, due to the complex interdependencies among CT acquisition and reconstruction parameters, traditional optimization methods rely on exhaustive testing of combinations of these parameters, which is often impractical. This study introduces a novel methodology that combines virtual imaging tools with reinforcement learning to optimize CT protocols more efficiently. Human models with liver lesions were imaged using a validated CT simulator and reconstructed with a novel CT reconstruction toolkit. The optimization parameter space included tube voltage, tube current, reconstruction kernel, slice thickness, and pixel size. The optimization process was performed using a Proximal Policy Optimization (PPO) agent, which was trained to maximize an image quality objective, specifically the detectability index (d') of liver lesions in the reconstructed images. Optimization performance was compared against an exhaustive search performed on a supercomputer. The proposed reinforcement learning approach achieved the global maximum d' across test cases while requiring 79.7% fewer steps than the exhaustive search, demonstrating both accuracy and computational efficiency. The proposed framework is flexible and can accommodate various image quality objectives. The findings highlight the potential of integrating virtual imaging tools with reinforcement learning for CT protocol management.

Lavsen Dahal, Mobina Ghojoghnejad, Dhrubajyoti Ghosh et al.

Virtual Imaging Trials (VIT) offer a cost-effective and scalable approach for evaluating medical imaging technologies. Computational phantoms, which mimic real patient anatomy and physiology, play a central role in VITs. However, the current libraries of computational phantoms face limitations, particularly in terms of sample size and diversity. Insufficient representation of the population hampers accurate assessment of imaging technologies across different patient groups. Traditionally, the more realistic computational phantoms were created by manual segmentation, which is a laborious and time-consuming task, impeding the expansion of phantom libraries. This study presents a framework for creating realistic computational phantoms using a suite of automatic segmentation models and performing three forms of automated quality control on the segmented organ masks. The result is the release of over 2500 new computational phantoms, so-named XCAT3.0 after the ubiquitous XCAT computational construct. This new formation embodies 140 structures and represents a comprehensive approach to detailed anatomical modeling. The developed computational phantoms are formatted in both voxelized and surface mesh formats. The framework is combined with an in-house CT scanner simulator to produce realistic CT images. The framework has the potential to advance virtual imaging trials, facilitating comprehensive and reliable evaluations of medical imaging technologies. Phantoms may be requested at https://cvit.duke.edu/resources/. Code, model weights, and sample CT images are available at https://xcat-3.github.io/.

Wanyi Fu, Shobhit Sharma, Ehsan Abadi et al.

Objective: This study aims to develop and validate a novel framework, iPhantom, for automated creation of patient-specific phantoms or digital-twins (DT) using patient medical images. The framework is applied to assess radiation dose to radiosensitive organs in CT imaging of individual patients. Method: From patient CT images, iPhantom segments selected anchor organs (e.g. liver, bones, pancreas) using a learning-based model developed for multi-organ CT segmentation. Organs challenging to segment (e.g. intestines) are incorporated from a matched phantom template, using a diffeomorphic registration model developed for multi-organ phantom-voxels. The resulting full-patient phantoms are used to assess organ doses during routine CT exams. Result: iPhantom was validated on both the XCAT (n=50) and an independent clinical (n=10) dataset with similar accuracy. iPhantom precisely predicted all organ locations with good accuracy of Dice Similarity Coefficients (DSC) >0.6 for anchor organs and DSC of 0.3-0.9 for all other organs. iPhantom showed less than 10% dose errors for the majority of organs, which was notably superior to the state-of-the-art baseline method (20-35% dose errors). Conclusion: iPhantom enables automated and accurate creation of patient-specific phantoms and, for the first time, provides sufficient and automated patient-specific dose estimates for CT dosimetry. Significance: The new framework brings the creation and application of CHPs to the level of individual CHPs through automation, achieving a wider and precise organ localization, paving the way for clinical monitoring, and personalized optimization, and large-scale research.

Fakrul Islam Tushar, Vincent M. D'Anniballe, Rui Hou et al.

Purpose: To design multi-disease classifiers for body CT scans for three different organ systems using automatically extracted labels from radiology text reports.Materials & Methods: This retrospective study included a total of 12,092 patients (mean age 57 +- 18; 6,172 women) for model development and testing (from 2012-2017). Rule-based algorithms were used to extract 19,225 disease labels from 13,667 body CT scans from 12,092 patients. Using a three-dimensional DenseVNet, three organ systems were segmented: lungs and pleura; liver and gallbladder; and kidneys and ureters. For each organ, a three-dimensional convolutional neural network classified no apparent disease versus four common diseases for a total of 15 different labels across all three models. Testing was performed on a subset of 2,158 CT volumes relative to 2,875 manually derived reference labels from 2133 patients (mean age 58 +- 18;1079 women). Performance was reported as receiver operating characteristic area under the curve (AUC) with 95% confidence intervals by the DeLong method. Results: Manual validation of the extracted labels confirmed 91% to 99% accuracy across the 15 different labels. AUCs for lungs and pleura labels were: atelectasis 0.77 (95% CI: 0.74, 0.81), nodule 0.65 (0.61, 0.69), emphysema 0.89 (0.86, 0.92), effusion 0.97 (0.96, 0.98), and no apparent disease 0.89 (0.87, 0.91). AUCs for liver and gallbladder were: hepatobiliary calcification 0.62 (95% CI: 0.56, 0.67), lesion 0.73 (0.69, 0.77), dilation 0.87 (0.84, 0.90), fatty 0.89 (0.86, 0.92), and no apparent disease 0.82 (0.78, 0.85). AUCs for kidneys and ureters were: stone 0.83 (95% CI: 0.79, 0.87), atrophy 0.92 (0.89, 0.94), lesion 0.68 (0.64, 0.72), cyst 0.70 (0.66, 0.73), and no apparent disease 0.79 (0.75, 0.83). Conclusion: Weakly-supervised deep learning models were able to classify diverse diseases in multiple organ systems.

Rafael B. Fricks, Justin Solomon, Ehsan Samei

Imaging phantoms are test patterns used to measure image quality in computer tomography (CT) systems. A new phantom platform (Mercury Phantom, Gammex) provides test patterns for estimating the task transfer function (TTF) or noise power spectrum (NPF) and simulates different patient sizes. Determining which image slices are suitable for analysis currently requires manual annotation of these patterns by an expert, as subtle defects may make an image unsuitable for measurement. We propose a method of automatically classifying these test patterns in a series of phantom images using deep learning techniques. By adapting a convolutional neural network based on the VGG19 architecture with weights trained on ImageNet, we use transfer learning to produce a classifier for this domain. The classifier is trained and evaluated with over 3,500 phantom images acquired at a university medical center. Input channels for color images are successfully adapted to convey contextual information for phantom images. A series of ablation studies are employed to verify design aspects of the classifier and evaluate its performance under varying training conditions. Our solution makes extensive use of image augmentation to produce a classifier that accurately classifies typical phantom images with 98% accuracy, while maintaining as much as 86% accuracy when the phantom is improperly imaged.